1. Field of the Invention
The present invention relates to methods for performing radiosurgery on a patient using microbeam radiation.
2. Description of the Related Art
Nearly two decades ago, a radiosurgery method was patented by Slatkin et al. (see U.S. Pat. No. 5,339,347, the disclosure of which is incorporated herein by reference). This radiosurgery method employs sub-millimeter beams of X-rays, termed microbeams. An advantageous feature of this radiosurgery technique is that the microbeams, while successfully destroying targeted diseased tissue, do not destroy the functionality of normal healthy tissue surrounding the target. Scientific studies using cell cultures and animal models show that although the normal tissue cells directly in the path of a microbeam are destroyed, the region of destruction is sufficiently small in width that the adjacent normal tissue is capable of healing the damaged region (see Dilmanian et al., Experimental Hematology, Vol. 35, 2007, pp. 69-77, the disclosure of which is incorporated herein by reference). Normal tissue heals when microbeams are less than 700 um in size (see Dilmanian et al., Proceedings of the National Academy of Sciences, Vol. 103, 2006, pp. 9709-9714, the disclosure of which is incorporated herein by reference). Diseased tissue is destroyed by cross firing from other directions, thereby creating sufficiently broad regions of damage that a healing response by adjacent tissue cannot be mounted.
Unfortunately, the great promise of microbeam radiosurgery has yet to be realized. There are two major problems. First, the only source of microbeam radiation capable of providing sufficient dose rate for radiosurgery until now has been a synchrotron. A synchrotron is a very large and expensive device. The synchrotron source which has been used for most microbeam radiosurgery studies is the European Synchrotron Radiation Facility located in Grenoble, France. The storage ring associated with this synchrotron is 300 m in diameter, and the facility cost approximately $900 M to construct. These characteristics of a synchrotron source are prohibitive.
This first problem is likely to be resolved by a new type of radiation source which utilizes the physical phenomenon of inverse Compton scattering to generate high energy X-ray photons. Such a source promises to provide the necessary dose rate, while requiring a much smaller footprint (less than 5 m in diameter) and much lower cost to construct (approximately $15 M) than a synchrotron (see Adler et al., U.S. patent application Ser. No. 13/453,338, the disclosure of which is incorporated herein by reference).
The second problem with conventional microbeam radiosurgery is the restriction of the X-ray photons comprising the microbeams to energies less than 200 keV. This restriction arises from the requirement that the dose deposition in tissue have a lateral profile (i.e., a profile in a direction orthogonal to the direction of beam propagation) with very sharp edges; that is, the lateral energy deposition in tissue must fall from the peak value abruptly (see Dilmanian et al., Experimental Hematology, cited above).
Referring to FIG. 1, the percentage lateral dose profile 10 in tissue required by conventional microbeam radiosurgery is shown. (Note: A percentage dose profile is obtained from a dose profile by dividing the dose at all positions by the maximum dose in the profile, and multiplying by 100.) It is preferred that the transition 14 from the peak dose value 12 to the valley dose value 16 have an 80% to 20% fall length of no more than a few tens of microns.
A percentage lateral dose profile such as shown in FIG. 1 requires incident photons of less than 200 keV because of the physical process known as Compton scattering. Compton scattering is the primary mechanism by which incident X-ray photons with energies between 100 keV and 10 MeV interact with the atoms comprising the tissues of a patient.
Referring to FIG. 2, the physical phenomenon of Compton scattering is shown. When a high energy photon 20 collides with a low energy atomic electron 22, the result is an ionized high energy electron 24 and a scattered reduced energy photon 26. Most energy deposition within the tissue of a patient is a result of secondary collisions of the high energy electron 24 with other atoms in the patient. The higher the initial energy of the electron 24, the farther the electron 24 can travel. In order to keep the width of energy deposition less than a few tens of microns within the patient, the incident X-ray photon 20 must have energy less than 200 keV.
Referring to FIG. 3, the percentage lateral dose profile associated with a 200 keV incident X-ray beam is shown. The percentage lateral flux profile 31 of the incident X-ray beam in air before striking the patient is extremely sharp, having a transition region 35 with an 80% to 20% fall length of 5 um. The associated percentage lateral dose profile 30 at a depth of 1 cm in the patient is also relatively sharp, having a transition region 34 from the peak dose value 32 to the valley dose value 36 with an 80% to 20% fall length of 25 um. (The percentage lateral dose profile 30 is obtained from Monte Carlo calculations of the Compton scattering process in water, which is a good model for the tissues of a patient.)
Referring to FIG. 4, the percentage lateral dose profile associated with a 400 keV incident X-ray beam is shown. The percentage lateral flux profile 41 of the incident X-ray beam in air before striking the patient is again very sharp, having a transition region 45 with an 80% to 20% fall length of 5 um. The associated percentage lateral dose profile 40 at a depth of 1 cm in the patient is not sharp, however, having a transition region 44 from the peak dose value 42 to the valley dose value 46 with an 80% to 20% fall length of 110 um.
Referring to FIG. 5, the percentage lateral dose profile associated with a 2 MeV incident X-ray beam is shown. The percentage lateral flux profile 51 of the incident X-ray beam in air before striking the patient is sharp, having a transition region 55 with an 80% to 20% fall length of 5 um. The associated percentage lateral dose profile 50 at a depth of 1 cm in the patient is very broad, having a transition region 54 from the peak dose value 52 to the valley dose value 56 with an 80% to 20% fall length of 275 um.
Requiring X-ray photon energies to be less than 200 keV results in insufficient dose to tissues deep within a patient. Such low energy photons are quickly absorbed by tissues near the surface of the body.
Referring to FIG. 6, the percentage dose profiles along the direction of beam propagation (i.e., in the direction of depth into the patient) for various X-ray photon energies are shown. The percentage depth dose profiles 62, 64, and 66 are those of X-ray photons of 200 keV, 400 keV, and 2 MeV, respectively. For all curves, the beam physical size is 500 um in diameter. It can be seen from FIG. 6 that the 2 MeV beam penetrates much deeper into a patient than the 200 keV and 400 keV beams. In general, the higher the photon energy, the deeper the beam penetrates into a patient.